Generally, in connection with the oral administration of substances which are difficultly soluble in the digestive fluids, such as the anti-diabetic substances mentioned below, the following problems arise: in many cases the active substance can only be partly absorbed, and greatly fluctuating blood levels of the active substance may occur inter- and intra-individually. However, in oral anti-diabetic agents, the start of the activity and the duration of the activity are also of particular importance since the activity should be matched to the blood glucose levels caused by the intake of food. This is not the case with the previously available preparations of anti-diabetic agents in which the effect of the substance and physiological insulin requirements in accordance with the intake of food cannot be reliably matched to one another in terms of time. The activity of the substance often occurs too late: frequently the maximum effect is only achieved at a time at which the blood glucose values are already dropping, even without medication, after the intake of food. Then, the activity of the substance continues even when the blood glucose has returned to its initial level (see Berger, in Pelzer and Froesch, Diabetische Enteropathie, Hypoglykamien, Verlag Hans Huber, Bern-Stuttgart-Wien 1974).
Attempts have been made to synchronize the hypoglycemic activity of a sulfonyl urea with the increase in blood glucose caused by food intake by taking the sulfonyl urea at a suitable time before the meal. However, it was then found that administration of the active substance thirty minutes before the meal did not result in a satisfactory improvement in activity [see Sartor et al., Eur. J. Clin. Pharmacolog. 21, 403 to 408 (1982)], partly because of the longer duration of activity mentioned above. Furthermore, a specific time difference between the taking of the medicine and the taking of food can only be reliably monitored in a clinic.
Attempts have also been made to solve these problems in the case of substances which are difficultly soluble in the digestive fluids by attempting to optimize the dissolution rate of the active substance, difficultly soluble per se, in the development of the galenic preparations. This was done, for example, by increasing the surface area of the active substance. Thus, German Patent No. 2,348,334 discloses a preparation form in which the active substance (also a hypoglycemic substance) is present with a particle surface area of from 3 to 10 m.sup.2 /gm in the presence of a wetting agent. However, this objective was also supposed to be achieved by applying the active substance in dissolved form to a substrate or carrier with the largest possible surface area and then removing the solvent [cf. H. Rupprecht, Acta Pharm. Technol. 26/1, pages 13 ff. (1980)].
Furthermore, attempts have been made to improve the dissolution rate by adding salt-forming agents (see German Offenlegungsschrift No. 31 24 090). However, to improve the solubility and the dissolution rate, solid dispersions were also produced. They consisted of the active substance and one or more water-soluble carriers, possibly combined with surface-active substances. To prepare these dispersions, a homogeneous melt is prepared from the active substance or possibly a salt thereof and a carrier (see German Offenlegungsschrift No. 2,355,743). In another process, the active substance and carrier are dissolved in a common solvent, and then the solvent is eliminated. The water soluble carriers used are, inter alia, polyvinylpyrrolidone or polyethylene glycols [see H. R. Merkle, Acta Pharm. Technol. 27/4, pages 193 ff. (1981); and W. L. Chiou, S. Riegelmann, J. Pharm. Sci. 60/9, 1281 ff. (1971)].
If the methods in the literature described below are used to produce preparations containing anti-diabetic substances, a better dissolution rate for the active substance, such as gliquidone, is scarecely obtained: the salt formation itself does not result in an increase in the dissolution rate [see Table 7, Example (c) below], and the application of active substance, such as gliquidone, to a carrier alone (see Example on page 10 below) does not produce the desired result either. In corresponding tests, which will be described in more detail hereinafter, the dissolution rate was determined, and in the case of gliquidone it was found to be no greater than the dissolution rates shown by known gliquidone-containing preparations.